Project Summary/Abstract Continuing support is requested for years 41-46 of the Yale Predoctoral Training Program in Human Genetics and Genomics. The program constitutes 44 trainers, the majority of whom are primary or secondary appointees in the Department of Genetics at the School of Medicine. Virtually all of the trainees over the last funding period have been matriculated in the Molecular Cell Biology, Genetics & Development Track (MCGD) in Biological and Biomedical Sciences at Yale. The proposed training program is focused on the use of genetic, genomic and computational approaches to understand human biology and disease. Training encompasses three core domains: 1) The genetics of human health and disease, encompassing disease gene discovery and the interpretation of human genetic variation; 2) Computational approaches to obtain biological insights from complex genomic datasets, both in human and model systems; and 3) Experimental studies in model organisms to understand how human genetic variation influences human biology and disease. Training faculty include investigators who are world leaders in each of these domains. This integrated training environment provides trainees with broad exposure to genetics, genomics and computational biology, and a rich training environment that prepares them for careers in science. Students admitted into the program have strong scientific backgrounds and research experience with high academic achievement. First year students are supported by Yale. Students are then supported by the training grant in years 2 and 3, and thereafter by funds in Training Faculty laboratories until graduation. Training in the first year includes formal course work focused on genetics, genomics and data analysis, as well as research rotations leading to selection of the thesis advisor and laboratory. In the second year, students complete course work and take a qualifying exam in which they must demonstrate mastery of genetics and defend two written research proposals. Subsequent years are devoted to dissertation research, development of experimental and analytic skills, and skills in written and oral presentation, leading to preparation and publication of the thesis work. In addition, students engage in supervised teaching experiences. The students also participate in Program-specific activities, including a Program Retreat, a Program Symposium, dedicated Research-in-Progress talks, and a Program Seminar Series. These activities provide students with targeted mentoring and career development opportunities and will help them develop a professional network of peers and senior colleagues that they can draw upon throughout their careers. Support is requested for 5 years for 7 Ph.D. students per year. Trainees are highly successful in completing their Ph.D. thesis work, publishing their work in high-impact journals, and the vast majority continue to contribute to science after leaving the program.